1. Field of Invention
The present invention relates to a novel process for preparing the alkali metal salts of an amino acid from the corresponding mineral acid salts. More specifically, the present invention relates to novel solid phase alkali metal salts of a cephalosporin antibiotic and to a process for preparing the cephalosporin alkali metal salts substantially free of impurities, from the corresponding hydrohalide salts
2. Information Disclosure
The cephalosporin antibiotic 7-[2-(2-amino-1,3-thiazol-4-yl)-2-methoxyimino)acetamido]-3-[(fur-2-ylcarb onyl)thiomethyl]-3-cephem-4-carboxylic acid (also named 7-[2-(2-amino-4-thiazolyl-2-methoxyimino)-acetamido]-3-[2-(furanylcarbonyl thiomethyl)-8-oxo-5-thia-1-azabicyclo-[4,2,0]oct-2-ene-1-carboxylic acid) of formula I, its alkali metal, alkaline earth metal and amine salts of the carboxylic acid group, and easily hydrolyzable ester groups thereof are described and claimed in Labeeuw et al., U.S. Pat. No. 4.464.367. This cephalosporin free acid compound of formula I is now known by the generic name ceftiofur.
These patented free acid and cationic metal and amine salt and ester forms of this cephalosporin antibiotic are somewhat unstable chemically and are obtained as amorphous compounds which are difficult to purify, and are less desirable to work with in manufacturing pharmacuetical formulations containing them.
Methods for the conversion of cephalosporin acids to their corresponding sodium salts are known. U.S. Pat. No. 4,224,371 describes the preparation and crystallization of the crystalline sodium salt from mixing cefotaxime and sodium acetate in aqueous alcohols. U.S. Pat. No. 3,840,535 discloses the use of sodium 2-ethylhexanoate to prepare the sodium salt of cephalosporins.
Crystalline hydrohalide salts of ceftiofur are described in European Patent Application 85307417.7, published May 7, 1986 (Publication Number 0180372).
The use of polyvinylpyridine as a hydrogen chloride scavenger during cephalosporin ring cleavage reactions is described in U.S. Pat. No. 4,289,695 (1981).
A brochure, entitled "Pyridine Functionality in Polymer Form," published by Reilly Tar and Chemical Corporation, Indianapolis, IN, describes the use of derivatives of polyvinylpyridine as acid scavengers.